Vitamin K2

[Blossom]

I also thought menatetrone was k2 ( mk4)
not menaquinone
I hope Imtaking the correct one

It seems they may be used interchangeably/are synonyms.
Menatetrenone vs Menaquinone - What's the difference?

 

[Elderflower j58]

No please never stop linking info,
I just got in abit of a panic about k2
and my response came across brusque.
I'm always very grateful for your input.

@Blossom

 

[Blossom]

No please never stop linking info,
I just got in abit of a panic about k2
and my response came across brusque.
I'm always very grateful for your input.

@Blossom

No you didn't sound brusque, not at all! I've been known to panic at times too.

 

[Elderflower j58]

@Blossom

For all my research I can't even spell
The bloody word properly.
I've just disolved into manic
Brain mush.

 

[Blossom]

@Blossom

For all my research I can't even spell
The bloody word properly.
I've just disolved into manic
Brain mush.

I just thought you probably didn't have your reading glasses on at the time. That's my excuse when I misspell something. Seriously though some of these words get a bit ridiculous when you're not a scientist.

 

[Mito]

Yeah but I need to be sure,I have clogged arteries.
I'm just fed up with all the confusion.

“MK-4 is taken up by our tissues very rapidly after we consume it. While it hasn’t been studied as carefully as MK-7, it may be less effective than MK-7 at reaching liver and bone but more effective at reaching most other tissues. This would make it better at protecting those tissues from calcium deposits and cancer development and supporting sex hormone production through its direct actions within our sex organs.”

https://chrismasterjohnphd.com/2016/12/09/the-ultimate-vitamin-k2-resource/

 

[Arrade]

At the end of the day both will work well

 

[Elderflower j58]

“MK-4 is taken up by our tissues very rapidly after we consume it. While it hasn’t been studied as carefully as MK-7, it may be less effective than MK-7 at reaching liver and bone but more effective at reaching most other tissues. This would make it better at protecting those tissues from calcium deposits and cancer development and supporting sex hormone production through its direct actions within our sex organs.”

View attachment 9216
https://chrismasterjohnphd.com/2016/12/09/the-ultimate-vitamin-k2-resource/

Thanks for this mito makes it a bit easier.
Would I still need to take k1 as I take aspirin
Or will menatetrenone cover normal coagulation.

 

[Mito]

Would I still need to take k1 as I take aspirin
Or will menatetrenone cover normal coagulation.

I believe all forms support blood clotting but.....from Masterjohn’s The Ultimate Vitamin K2 Resource

MK-7 Supports Blood Clotting Better Than K1
MK-7 is not just three times better than K1 at reaching bone; it’s also five times better at supporting blood clotting (Schurgers, 2007). This may be because the greater fat-solubility of MK-7 makes it hold on more tightly to the membranes within liver cells, making it stay active in the liver much longer rather than being released and broken down (Shearer, 2008). The liver is where clotting proteins are made, so more extended activity in the liver would explain why MK-7 could better support blood clotting. If this is correct, other long-chain MKs such as MK-8 and MK-9 probably share this property as well.

 

[Arrade]

I believe all forms support blood clotting but.....from Masterjohn’s The Ultimate Vitamin K2 Resource

MK-7 Supports Blood Clotting Better Than K1
MK-7 is not just three times better than K1 at reaching bone; it’s also five times better at supporting blood clotting (Schurgers, 2007). This may be because the greater fat-solubility of MK-7 makes it hold on more tightly to the membranes within liver cells, making it stay active in the liver much longer rather than being released and broken down (Shearer, 2008). The liver is where clotting proteins are made, so more extended activity in the liver would explain why MK-7 could better support blood clotting. If this is correct, other long-chain MKs such as MK-8 and MK-9 probably share this property as well.

I wonder why Mk7 is the go to, compared to mk8 or mk9

 

[Amazoniac]

I suggest people to read Zeus' post on the first page.

All this menaquinone discussion distracts from the fact that we're adapted to get most of our vit K as K1.
MK-7 without enough K1 is a problem. MK-4 is not but the doses need to be high and I don't know the consequences of adapting to it, if frequent small feedings (such as its presence in milk) are better than brutal doses, and what needs to be increased along.

Vit K2 in chronic high doses delivered at once are also a little concerning. It's more like a therapeutic approach and I have no idea how the body adapts to it when the person insists on elevated daily doses. I remember Tarmander experiencing some problems with it, I have the impression it's something slightly stressful.
Between K1, MK-4 and MK-7, K1 is the most saturated of them, and if I recall it correctly, the liver is its main target when absorbed and circulated in such form. Rayzord posted about vitamin A supplements being easily oxidized during digestion (plug), and perhaps the same occurs with K2 as vvell. In this regard, K1 will probably be more stable. It's also protective because if you consume enough greens, you'll have these quinones all throughout the entire digestive tract.
When you apply a K2 supplement topically, some will eventually reach the liver, but there won't be the normal distribution that occurs with digestion, in which nutrients first pass through the liver and only then reach other tissues. Since most products available contain different menaquinones, MK-4 is rapidly taken up by other tissues and the liver will get the other menaquinones and MK-4 possibly only when other tissues already have an excess of it.
I know there are trials with it to treat liver cancer but there are a lot of therapies that involve oxidative stress to restore respiration, something unnecessary or even slightly detri and mental for maintenance. I think plenty of greens and a little K2 is a safer approach. In foods these vitamins are protected, therefore they're more resistant to degradation before absorption.

From Protein Folding to Blood Coagulation: Menaquinone as a Metabolic Link between Bacteria and Mammals

"Low concentrations of vitamin K2 can be found in dairy, meat, and fermented foods like nato [27], but makes up only 10% of total dietary vitamin K intake. While K1, found in a variety of green leafy plants and vegetable oils, is present in much higher amounts, it is not readily absorbed in the intestines as it is strongly bound to vegetable fiber [28]. Vitamin K is not transported by specific plasma carrier proteins like other fat‐soluble vitamins, but is instead shutled by lipoproteins. The small fraction of K1 that is absorbed is almost exclusively incorporated into the triacylglycerol‐rich lipoprotein (TGRLP) fraction, while dietary K2 is associated with low‐density lipoprotein (LDL) fraction [29]. These divergent pathways would deliver large amounts of K1 to the liver, but efficient delivery to extrahepatic tissues would only occur for K2. Measurements of the concentrations of vitamins K in various tissues mostly back this up, showing that K1 levels are low in the brain, kidneys, and lungs but high in the liver, heart, and pancreas; K2 (in the form of M and K and 4) was found to be in high concentration in the brain, kidneys, and pancreas but in low concentration in the liver, heart, and lungs. As for longer chain K2s, MK6‐11 were found in the liver and trace amounts of MK6‐9 were found in the heart and pancreas [30]. MK10 and MK11 may be major contributors to the hepatic pool of K2 [26], and the presence of these long‐chain MKs again raise the possibility that the commensal population of colonic bacteria may somehow contribute to overall vitamin K levels in the host, as analysis of tissue samples has only shown the ability to synthesize MK‐4 from K1. However, the presence of potential homologs for other prenyl diphosphate synthases in the genome further suggests that humans may be capable of producing longer chain MKs as well. Overall the data clearly indicate that dietary K1 is a major contributor to vitamin K levels in the body, but a full accounting of its sources has yet to emerge."

"The degree of lipophilicity in the tails most likely dictates mobility of the quinones in the membrane, with the partially unsaturated isoprenyl tail of MK allowing for greater freedom of movement compared to the mostly saturated chain of K1."

"While the flexibility of K2s is crucial to all of these redox‐driven processes, short circuits occur wherein reduced menaquinones donate their electrons to "inappropriate" acceptors like oxygen. Such reactions result in the production of reactive oxygen species and can lead to massive damage to proteins and the NA [40, 41], underlining the importance of properly regulating the expression and distribution of MKs."

"After passing electrons onto the appropriate acceptors, MK is oxidized to its inactive, oxidized form." "To recharge and replenish their redox‐active pool of MKs, mammals have evolved enzymes capable of reducing of vitamin K 2,3‐epoxide (KO) to vitamin K and vitamin K hydroquinone (KH2)." "While the enzymatic activity of vitamin K epoxide reductase (VKOR) had first been assayed in 1974 and VKOR had long been known to be the target of the anticoagulant warfarin, identiication of the enzyme responsible for the regeneration of vitamin K did not come until 2004 [42, 43]."
"VKOR contains a total of four conserved cysteines, two of which are present in a C‐X‐X‐C motif characteristic of redox‐active thioredoxins. These two cysteines (C132 and C135) have been shown to be essential for the reduction of vitamin KO to vitamin K and vitamin KH2 using
purified VKOR [46]."
"Early studies with microsomal fractions indicated that protein disulide isomerase (PDI) might be an important source of electrons for VKOR [55], which is consistent with PDI's localization to the ER lumen. PDI can act as an electron acceptor by interacting with proteins containing multiple cysteine residues. By accepting electrons from such proteins, disulide bonds form between these cysteines, which can serve to stabilize or activate these substrates. Following this reaction, the reduced form of PDI is free to donate its electrons to other partner proteins. Studies confirmed that PDI could stimulate VKOR's reductive activity and went on to suggest that VKOR and PDI may even form a complex in the ER membrane [56]. In other words, the reduction of vitamin KO may be driven by the formation of disulide bonds in the ER lumen. Such a mechanism appears to contribute to the overall redox homeostasis within the ER [57] and has also been suggested to operate in plants as well [58, 59]."​

This must involve glutathione, B-vitamins (especially niacin and riboflavin), vit C, E and selenium somehow. And colossal doses of K2 are probably safer if you increase those along.

The role of glutathione in disulphide bond formation and endoplasmic-reticulum-generated oxidative stress

"[..]the lumen of the endoplasmic reticulum (ER) contains a relatively higher concentration of oxidized glutathione (GSSG; Hwang et al, 1992). This allows the formation of native disulphide bonds in the ER through a complex process involving not only disulphide-bond formation, but also the isomerization of non-native disulphide bonds. Both reactions can be catalysed by protein disulphide isomerase (PDI) and possibly other oxidoreductases that share common domains with PDI (for a recent review, see Ellgaard & Ruddock, 2005). PDI has two active sites, both of which are characterized by the presence of a CGHC motif, which either forms a disulphide for the enzyme to become active as an oxidase, or a dithiol for the enzyme to act as an isomerase. GSSG is widely believed to be involved in the oxidation of PDI, but it has been shown that the ER flavoprotein Ero1 catalyses the oxidation of PDI in vivo and in vitro (Frand & Kaiser, 1998, 1999; Pollard et al, 1998; Tu et al, 2000; Tu & Weissman, 2002). These results indicate that the process of disulphide-bond formation might occur independently of GSSG. However, this does not explain the fact that, in the ER, the ratio of reduced to oxidized glutathione ([GSH]:[GSSG]) is optimal for disulphide-bond formation (Lyles & Gilbert, 1991). Recently, it has been suggested that GSH might have a role in ensuring the ER oxidoreductases are maintained in a reduced state so that they can catalyse reduction or isomerization reactions (Chakravarthi & Bulleid, 2004; Jessop & Bulleid, 2004; Molteni et al, 2004). It is still not known why an oxidizing balance of glutathione is required in the ER or how this balance is maintained. In addition to a role in disulphide-bond formation, it has been suggested that glutathione provides a redox buffer against ER-generated oxidative stress."​

Role of quinones on the ascorbate reduction rates of S-nitrosogluthathione

"Quinones can be enzymatically reduced by flavoenzymes. Some of these can catalyze a one electron reduction of quinones such as NADPH-cytochrome P450 reductase, NADH-cytochrome b5 reductase or NADH/NAD(P)H dehydrogenase [7, 8]. Xanthine oxidase catalyzes the reduction by one and two electrons of quinones [9, 10]. The catalytic enhancement of ascorbate oxidation by quinones has been previously observed, including its dependence on the quinone one-electron redox potential (E17) [11]. In addition, we have previously observed that quinones enhance the rates of ascorbate and xanthine/xanthine oxidase reduction of nitric oxide (NO) [12, 13]"

"A constant steady state concentration of the ascorbyl radical has been observed in previous works during the quinone-enhanced, [60] as well as in the iron- and methylene blue-catalyzed, [61] ascorbate oxidation."​

Which is why it's preferable to get most of vit K from leaves and the rest from K2 sources or supplements in smaller amounts. Another safe approach would be to take a little at a time, tiny doses throughout the day.

Vitamin K2 in Electron Transport System: Are Enzymes
Involved in Vitamin K2 Biosynthesis Promising Drug Targets?

"A majority of Gram-negative organisms utilize ubiquinone (Q) under aerobic conditions, and menaquinone under anaerobic conditions in their electron transport systems. Most importantly, the electron transport chain in humans does not utilize menaquinone. Clearly, the electron transport chain is a central component in the production of ATP and the subsequent growth of bacteria (Figure 3). Therefore, inhibitors of menaquinone biosynthesis or specific inhibitors of enzymes associated with electron transport systems have great potential for the development of novel and selective drugs against multi-drug resistant (MDR) Gram-positive pathogens."

"Menaquinones are the predominant isoprenoid lipoquinones of Gram-positive bacteria, whereas Gram-negative bacteria such as E. coli and close relatives (i.e., enterobacteria) use menaquinone (MK), demethylmenaquinone (DMK), and ubiquinone (Q) in their electron transport chains (see Figure 1)."
Some antibiotics target this.​

Rosacea, inflammation, and aging: The inefficiency of stress

"When mitochondria are damaged, active cells produce increased amounts of lactic acid, even in the presence of adequate oxygen. Otto Warburg identified this kind of metabolism, aerobic glycolysis, as an essential feature of cancer, and showed that it could be produced by stress, ionizing radiation, carcinogenic toxins, and even by a simple oxygen deficiency. Other investigators around the same time showed that lactic acid produces vasodilation (for example, in the cornea), and more recently it has been shown to promote the development of fibrosis, and it has been called a "phlogogen," a promoter of inflammation.

Riboflavin, vitamin B2, is an essential component of the mitochondrial respiratory enzymes, and it is very easily destroyed by light (blue light and especially ultraviolet). When it is excited by high energy light, it can spread the damage to other components of the mitochondria, including the cytochromes and the polyunsaturated fatty acids. The other B vitamins are affected when riboflavin's actions are disturbed.

Vitamin K is also extremely light sensitive, and it interacts closely with coenzyme Q in regulating mitochondrial metabolism. For example, mitochondrial Complex-I, NADH-ubiquinone reductase, is probably the most easily damaged part of the mitochondrion, and it is protected by vitamin K. Vitamin E, coenzyme Q, and the polyunsaturated fatty acids are also light sensitive, and they are more susceptible to free radical damage when vitamin K is deficient."​

--
Chris wrote:
"Until we have well designed trials comparing the ability of different MKs to support different health outcomes in humans, it makes sense to rely on what we know generally about how lipoproteins transport nutrients. This suggests K1 would best reach the liver, MKs 7-9 would best reach liver and bone, and MK-4 would best reach most other tissues."

 

[baccheion]

Slade what dosage were you running? I just purchased mk4 and plan to do 45 mg daily for this effect. @baccheion said to go 90, which is kinda expensive

Maybe 1.5 mg topically (Kuinone) 3x/day will work as well. 90 mg (30 mg 3x/day) was based on the osteoporosis study (ie, 45 mg / 45 kg or 1 mg/kg), your weight, and the amount in a megadose pill. 5 pills = 75 mg and wasn't quite enough.

 

[Arrade]

Maybe 1.5 mg topically (Kuinone) 3x/day will work as well. 90 mg (30 mg 3x/day) was based on the osteoporosis study (ie, 45 mg / 45 kg or 1 mg/kg), your weight, and the amount in a megadose pill. 5 pills = 75 mg and wasn't quite enough.

I'm going to try 45 mg orally for a month, with LEF once a day
I don't trust topical

 

[baccheion]

I'm going to try 45 mg orally for a month, with LEF once a day
I don't trust topical

How long do others say it takes to notice widening?

 

[Arrade]

How long do others say it takes to notice widening?

I know @sladerunner69 said 5mg for a year, Ivysaur said almost immediately which is eh, a few women on here noticed it after a few months.
A buddy of mine used it for 2 months along with a chewing gum and got results

 

[sladerunner69]

I know @sladerunner69 said 5mg for a year, Ivysaur said almost immediately which is eh, a few women on here noticed it after a few months.
A buddy of mine used it for 2 months along with a chewing gum and got results

I notice it forsure

 

[Arrade]

@Elderflower j58
Impact of menaquinone-4 supplementation on coronary artery calcification and arterial stiffness: an open label single arm study
This study shows women around the age of 69 used mk4 45 mg a day for a year and their coronary artery calcification actually increased by 14%.
Amazoniac already posted that the longer chains were better for arteries, and honestly I haven't seen much evidence mk4 helps.
I would suggest something like this:
https://www.amazon.com/Jarrow-Formu...6&sr=1-19&keywords=vitamin+k2#customerReviews

When people were supplemented with 200 mcg per day of MK-7 form of K2, the proteins that are dependent on Vitamin K2 were almost fully activated.
People aren't getting the results they want from Mk-7 because they only supplement 90mcg a day. Make sure to get at least 200mcg, possible 300-360 mcg.

 

[crestind]

I tried MK7 at around 80mcg every other day for maybe a week or two. I developed some odd stretch marks on my skin. I stopped taking it and after almost two months now it's basically gone away. No idea if cis or trans.

Been taking MK4 80mcg every day for a week or so and did notice the strange smooth teeth effect after a few days. There's like this slick sort of film covering the teeth. I feel like the saliva is every so slightly more viscous? This is all hard to quantify so take it all with a grain of salt. Downside I did develop a small ulcer in the mouth, not sure if related.

Given all the information on the various types of vitamin K, I speculate the ideal form that should be taken is K1, in fact, but I have not tested this. I believe the body is meant to convert the K1 to K2 MK4 and utilize it. If you take the MK4 directly, it is akin to taking preformed vitamin A or D which bypasses the body's natural regulatory processes for levels of these vitamins. In nature, preformed vitamin A and D is actually quite rare (how many people in ancient times spent their days supplementing nonsense like fermented cod liver oil?), and is almost certainly NOT how humans evolved to obtain the vitamins. A is meant to come from plants, and D is meant to come from sunlight exposure. This is made obvious by the fact that you can develop hypervitaminosis from A and D rich foods, but you cannot readily overdose on beta carotenes, or die rapidly from excessive sun exposure. In which case, I propose K1 is the same. It may be vitamin K1 and/or provitamin K2 MK4.

 

[Arrade]

I tried MK7 at around 80mcg every other day for maybe a week or two. I developed some odd stretch marks on my skin. I stopped taking it and after almost two months now it's basically gone away. No idea if cis or trans.

Been taking MK4 80mcg every day for a week or so and did notice the strange smooth teeth effect after a few days. There's like this slick sort of film covering the teeth. I feel like the saliva is every so slightly more viscous? This is all hard to quantify so take it all with a grain of salt. Downside I did develop a small ulcer in the mouth, not sure if related.

Given all the information on the various types of vitamin K, I speculate the ideal form that should be taken is K1, in fact, but I have not tested this. I believe the body is meant to convert the K1 to K2 MK4 and utilize it. If you take the MK4 directly, it is akin to taking preformed vitamin A or D which bypasses the body's natural regulatory processes for levels of these vitamins. In nature, preformed vitamin A and D is actually quite rare (how many people in ancient times spent their days supplementing nonsense like fermented cod liver oil?), and is almost certainly NOT how humans evolved to obtain the vitamins. A is meant to come from plants, and D is meant to come from sunlight exposure. This is made obvious by the fact that you can develop hypervitaminosis from A and D rich foods, but you cannot readily overdose on beta carotenes, or die rapidly from excessive sun exposure. In which case, I propose K1 is the same. It may be vitamin K1 and/or provitamin K2 MK4.

I like your point about K1.
I’ll say I’ve used 600 mcg mk7 no stretch marks, bones popped a lot though.
I’ve used 45 mg mk4 and so far I feel the test/energy increase. Noticed nothing on teeth though.
My guess would be stretch marked from growing bones though you didn’t really use much

 

[crestind]

Did you experience any changes to the face? I'm still intrigued by that user "gummybear" and his alleged widening face. My main interest in vitamin K is its potential in widening the dental arches naturally in conjunction with chewing fibrous leafy greens.

The stretch marks on my skin appeared after only two weeks, and it was only on my calves. I'm not sure that I could've grown enough to get stretch marks in such a short period. I would expect to see changes over the course of three months and on. I stopped taking MK7 for another reason, its only source is bacteria in the gut apparently (?) The bone popping you mention is kinda iffy. I'd seen nosebleeds mentioned twice as a side effect of MK7 too.